The Phase Diagram of the API Benzocaine and Its Highly Persistent, Metastable Crystalline Polymorphs
Abstract
:1. Introduction
2. Experimental
2.1. Materials
2.2. Adiabatic Calorimetry
2.3. Differential Scanning Calorimetry
2.4. Powder X-ray Diffraction
2.5. High-Pressure Differential Thermal Analysis
3. Results
3.1. The I→ II Transformation
3.2. The Thermal Expansion of Benzocaine
3.3. Heat Capacity, Entropy, Enthalpy, and Gibbs Free Energy Obtained via Adiabatic Calorimetry
3.4. Transition Temperatures Obtained under Pressure
4. Discussion
4.1. Stability of Benzocaine under Ordinary Pressure: Adiabatic versus DSC
4.2. Construction of the Pressure–Temperature Phase Diagram
4.2.1. High-Pressure Data and Its Triple Points
4.2.2. The Positions of the I–III and the III–L Equilibria
4.2.3. The Pressure–Temperature Phase Diagram
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Code (QQQAXG) | Form | T/K | Space Group | a | b | c | β,γ b | Vcell/Å3 | vspec/cm3 g−1 | Ref. |
---|---|---|---|---|---|---|---|---|---|---|
02 | I | 150 | P21/c | 8.198 | 5.430 | 19.592 | 91.35 | 871.9 | 0.7946 | [15] |
04 | I | 300 | P21/c | 8.257 | 5.501 | 19.956 | 91.70 | 906.0 | 0.8257 | [16] |
06 | I | 300 | P21/c | 8.257 | 5.501 | 19.956 | 91.70 | 906.0 | 0.8257 | [17] |
09 | I | 296 | P21/c | 8.250 | 5.501 | 19.950 | 91.73 | 905.0 | 0.8248 | [18] |
00 | II | 293 | P212121 | 5.307 | 8.222 | 20.869 | 910.6 | 0.8299 | [19] | |
01 | II | 293 | P212121 | 5.302 | 8.217 | 20.870 | 909.2 | 0.8287 | [20] | |
05 | II | 300 | P212121 | 5.311 | 8.242 | 20.904 | 915.0 | 0.8339 | [16] | |
07 | II | 300 | P212121 | 5.311 | 8.242 | 20.904 | 915.0 | 0.8339 | [17] | |
10 | II | 293 | P212121 | 5.309 | 8.236 | 20.866 | 912.4 | 0.8315 | [18] | |
03 | III | 150 | P21 | 8.188 | 10.639 | 20.476 | 99.37 | 1759.9 | 0.8020 | [16] |
08 | III | 150 | P21 | 8.188 | 10.639 | 20.476 | 99.37 | 1759.9 | 0.8020 | [17] |
13 | IV a | 298 | P21/c | 6.305 | 5.184 | 24.940 | 96.25 | 810.3 | 0.7385 | [14] |
Peaks I → II | Fusion | ||||||
---|---|---|---|---|---|---|---|
Sample | Mass/mg | T/K | ∆H/J g−1 | T/K | ∆H/J g−1 | T/K | ∆H/J g−1 |
TA instruments | |||||||
1 | 3.84 | 316.8 | 0.67 | 340.2 | 1.09 | 362.6 | 132.9 |
2 | 3.11 | 341.6 | 0.89 | 362.6 | 137.5 | ||
3 | 7.89 | 317.0 | 1.70 | 362.8 | 127.4 | ||
4 | 1.66 | 340.0 | 1.86 | 362.6 | 129.9 | ||
5 | 2.42 | 342.4 | 2.63 | 362.6 | 134.4 | ||
6 | 3.70 | 318.0 | 0.03 | 344.2 | 1.54 | 362.6 | 133.5 |
7 | 4.44 | 317.6 | 0.50 | 339.2 | 0.61 | 362.6 | 131.0 |
Perkin Elmer | |||||||
8 | 2.46 | 321.0 | 0.76 | 339.6 | 2.24 | 359.8 | 129.9 |
9 | 2.08 | 316.2 | 0.62 | 332.6 | 1.97 | 361.4 | 127.5 |
10 | 2.15 | 336.2 | 0.90 | 361.8 | 131.5 | ||
11 | 2.42 | 343.8 | 1.67 | 361.4 | 133.1 |
Equilibrium | T /K | ∆S /J g−1 K−1 | ∆H /J g−1 |
---|---|---|---|
III-II | 266.0 | 0.010225 | 2.7194 |
I-II | 319.5 | 0.011938 | 3.8146 |
II-L | 361.0 | 0.369514 | 133.412 |
Triple Point | Temperature/K | Pressure/Pa | |
---|---|---|---|
I–II–III | 154.0 | −307 × 106 | metastable |
III–II–v | 267.8 | 0.012 | metastable |
I–II–v | 316.6 | 2.4 | stable |
I–III–L | 326.1 | −198 × 106 | supermetastable |
III–L–v | 358.3 | 78 | supermetastable |
I–L–v | 359.5 | 83 | metastable |
II–L–v | 362.0 | 95 | stable |
I–II–L | 380.1 | 120 × 106 | stable |
III–II–L | 428.9 | 435 × 106 | metastable |
I–III–v | 639.3 | 7.4 × 106 | supermetastable |
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Rietveld, I.B.; Akiba, H.; Yamamuro, O.; Barrio, M.; Céolin, R.; Tamarit, J.-L. The Phase Diagram of the API Benzocaine and Its Highly Persistent, Metastable Crystalline Polymorphs. Pharmaceutics 2023, 15, 1549. https://doi.org/10.3390/pharmaceutics15051549
Rietveld IB, Akiba H, Yamamuro O, Barrio M, Céolin R, Tamarit J-L. The Phase Diagram of the API Benzocaine and Its Highly Persistent, Metastable Crystalline Polymorphs. Pharmaceutics. 2023; 15(5):1549. https://doi.org/10.3390/pharmaceutics15051549
Chicago/Turabian StyleRietveld, Ivo B., Hiroshi Akiba, Osamu Yamamuro, Maria Barrio, René Céolin, and Josep-Lluís Tamarit. 2023. "The Phase Diagram of the API Benzocaine and Its Highly Persistent, Metastable Crystalline Polymorphs" Pharmaceutics 15, no. 5: 1549. https://doi.org/10.3390/pharmaceutics15051549